The Pennsylvania Muscle Institute functions as a regional interdisciplinary Program Project for collaborative studies on normal and diseased cardiac, vascular smooth and skeletal muscle and on blood cell motility. The aims of the present proposal are to determine the distribution of myosin isoenzymes in different regions of the heart and within single cardiac cells through the use of histochemical methods and gel electrophoresis and to determine the effects of adrenergic agents on cardiac myosin. These investigations are an integral part of the overal objectives of the Program that includes studies of the development, molecular organization and function of the contractile and regulatory proteins, excitation-contraction coupling, intracellular ion movements, muscle mechanics and energetics and blood platelet transformation. Specialized techniques used include cryoultramicrotomy, enzyme histochemistry, freeze fracture, electron probe and electron energy loss analysis, conventional, scanning and high voltage electron microscopy, fluorescent antibody techniques, nuclear magnetic resonance, laser flash photolysis, dual wave spectroscopy. Various aspects of these techniques have been developed by the Program Project with the major objective of applying them for the better understanding of the pathophysiology of the changes in cardiac and vascular smooth muscle related to heart disease and high blood pressure. The present Proposal is expected to reveal how the distribution of myosin isoenzymes in different regions of the heart influence cardiac contractility and to establish the mechanism of long term adrenergic regulation of myosin isoenzymes and its effect on cardiac contraction.